rs1937750347

Variant names:

• chr3-122912030-T-C
• rs1937750347
• NM_001031702.4:c.2936A>G

Your query was ambiguous. Multiple possible variants found:

• chr3-122912030-T-C
• chr3-122912030-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001031702.4(SEMA5B):​c.2936A>G​(p.Asp979Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D979A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SEMA5B NM_001031702.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.41

Genes affected

SEMA5B (HGNC:10737): (semaphorin 5B) This gene encodes a member of the semaphorin protein family which regulates axon growth during development of the nervous system. The encoded protein has a characteristic Sema domain near the N-terminus, through which semaphorins bind to plexin, and five thrombospondin type 1 repeats in the C-terminal region of the protein. The protein product may be cleaved and exist as a secreted molecule (PMID: 19463192). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20884949).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA5B	NM_001031702.4	c.2936A>G	p.Asp979Gly	missense_variant	Exon 20 of 23	ENST00000357599.8	NP_001026872.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA5B	ENST00000357599.8	c.2936A>G	p.Asp979Gly	missense_variant	Exon 20 of 23	1	NM_001031702.4	ENSP00000350215.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000312 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.041	.;.;T;.;T;.;T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.14
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.16	T;T;T;T;.;T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.21	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.3	.;.;N;.;N;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.8	.;N;.;.;N;.;N
REVEL	Benign	0.095
Sift	Benign	0.33	.;T;.;.;T;.;T
Sift4G	Benign	0.49	.;T;T;T;T;.;T
Polyphen		0.0	.;.;B;.;B;.;.
Vest4		0.23, 0.25, 0.35, 0.26
MutPred		0.46		.;.;Gain of glycosylation at T978 (P = 0.0151);.;Gain of glycosylation at T978 (P = 0.0151);.;Gain of glycosylation at T978 (P = 0.0151);
MVP		0.50
MPC		0.35
ClinPred		0.81	D
GERP RS		4.8
Varity_R		0.21
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1937750347; hg19: chr3-122630877;